A recent federal report suggested that rigorous tests of condom effectiveness against sexually transmitted infections (STIs) are urgently needed. 1 To date, published studies have not described tests of condom effectiveness. Further, a search of the CRISP database revealed that studies of condom effectiveness have not yet been funded. The proposed study uses an innovative approach to testing condom effectiveness against penile-vaginal acquisition of a) Chlamydia, b) trichomoniasis, and c) any of three non-viral STIs (Chlamydia, trichomoniasis, and gonorrhea) (Aim 1). The negative sequelae of these infections are well documented. The infections also increase the odds of HIV acquisition and transmission. Because the protective value is highly likely to vary between men and women, the study will also test for moderating effects of sex (gender) on condom effectiveness (Aim 2). Based on a substantial amount of research conducted by the PI of the proposed study, it is also quite apparent that various forms of condom failure must be accounted for in tests of condom effectiveness. Therefore the study will quantify the loss of protective value attributable to these sources of failure (Aim 3). A final study aim is to determine the loss of protective value incurred as the frequency of condom use decreases from 100% (Aim 4). The sample will be 625 men and 625 women (>15 years of age) attending one of two clinics for the evaluation and treatment of an STI. Participants will be followed over 6 months. After initially being tested (using DNA amplification) and treated (using single-dose, directly observed therapy) for existing non-viral STIs, participants will learn how to use a Personal Digital Assistant to keep an electronic coital diary over the subsequent 6 months. This innovative method of data collection helps assure optimal validity of the assessed behaviors. A brief education session will also be provided. This session will promote the correct and consistent use of condoms during the study period thereby helping to ensure that an adequate number of participants are classified as "100%" users in the analyses. A 3-month follow-up screening will detect early reinfections or new infections. A 6-month follow-up period will also include re-screening for the three STIs. The study is adequately powered (>80%) to detect even modest effect sizes. Findings will be disseminated to inform public health policy and programs related to the use of condoms in the prevention of these common, non-viral STIs.